BACKGROUND: Many countries are facing overlapping epidemics of tuberculosis (TB) and diabetes mellitus (DM). Diabetes increases the overall risk of developing Tuberculosis (TB) and contributes to adverse treatment outcomes. Active screening for both diseases can reduce TB transmission and prevent the development of complications of DM. We investigated bi-directional TB-DM screening in Karachi, Pakistan, a country that ranks fifth among high TB burden countries, and has the seventh highest country burden for DM. METHODS: Between February to November 2014, community-based screeners identified presumptive TB and DM through verbal screening at private health clinics. Individuals with presumptive TB were referred for a chest X-ray and Xpert MTB/RIF. Presumptive DM cases had random blood glucose (RBS) tested. All individuals with bacteriologically positive TB were referred for diabetes testing (RBS). All pre-diabetics and diabetics were referred for a chest X-ray and Xpert MTB/RIF test. The primary outcomes of this study were uptake of TB and DM testing. RESULTS: A total of 450,385 individuals were screened, of whom 18,109 had presumptive DM and 90,137 had presumptive TB. 14,550 of these individuals were presumptive for both DM and TB. The uptake of DM testing among those with presumptive diabetes was 26.1% while the uptake of TB testing among presumptive TB cases was 5.9%. Despite efforts to promote bi-directional screening of TB and DM, the uptake of TB testing among pre-diabetes and diabetes cases was only 4.7%, while the uptake of DM testing among MTB positive cases was 21.8%. CONCLUSION: While a high yield for TB was identified among pre-diabetics and diabetics along with a high yield of DM among individuals diagnosed with TB, there was a low uptake of TB testing amongst presumptive TB patients who were recorded as pre-diabetic or diabetic. Bi-directional screening for TB and DM which includes the integration of TB diagnostics, DM screening and TB-DM treatment within existing health care programs will need to address the operational challenges identified before implementing this as a strategy in public health programs.